Performing real-time microscopy has been a vision of endoscopists since the very early phases of gastrointestinal endoscopy. Confocal endomicroscopy, an adaption of confocal laser scanning microscopy, and endocytoscopy, an adaption of white-light microscopy, have been introduced into the endoscopic armamentarium in the past decade. Both techniques yield on-site histological information. Multiple trials have demonstrated the ability of gastroenterologists to obtain and interpret microscopic images from the upper and lower gastrointestinal tract, and also the hepatobiliary-pancreatic system, during endoscopy. Such microscopic information has been successfully used in expert hands to minimize sampling error by 'smart', microscopically targeted biopsies and to guide endoscopic interventions. However, endomicroscopy is also unique in its ability to dynamically visualize cellular processes in their native environment free of artefacts. This ability enables fundamental insights into mechanisms of human diseases in clinical and translational science.